Gene therapy for Wiskott-Aldrich syndrome: preliminary results after treatment of the first patients.

KAAN BOZTUG; INES AVEDILLO DÍEZ; RICARDO A. DEWEY; MANFRED SCHMIDT; CHRISTOPH VON KALLE; SONJA NAUNDORF; KLAUS KUEHLKE; CHRISTOPH KLEIN

Kartause Ittingen, Germany

Jornada; XXIV. Jahrestagung der Arbeitsgemeinschaft Pädiatrische Immunologie.; 2007

Arbeitsgemeinschaft Pädiatrische Immunologie.

Wiskott-Aldrich syndrome is a complex primary immunodeficiency disorder associated with microthrombocytopenia, eczema, autoimmune phenomena and susceptibility to malignant lymphoma. Allogenic hematopoietic stem cell transplantation (HSCT) represents a curative approach but remains problematic in light of severe risks and side effects, in particular if no HLA-matched donor is available. More recently, extensive preclinical studies conducted by us and others have indicated that gene therapy may be a feasible and effective therapeutic option. The first hematopoietic stem cell gene therapy trial for Wiskott-Aldrich syndrome has been open for patient accrual since 2006. Two patients with classical, severe Wiskott-Aldrich syndrome for whom an HLA-matched donor was unavailable have been enrolled. Preliminary results on gene marking, efficacy, and functional reconstitution suggest that transplantation of retrovirally modified hematopoietic stem cells may be an alternative to conventional allogeneic bone marrow transplantation. Long-term follow up will be necessary to assess sustained correction of the hematopoietic system and to determine the risk-benefit ratio.